Remineralizing-mineralizing oral products containing discrete cationic and anionic agglomerate components and method of use

ABSTRACT

A solid oral product, e.g., chewing gum, lozenge, an edible foodstuff, and the like, which is useful for remineralizing subsurface dental lesions and/or mineralizing exposed dentinal tubules, contains (A) a discrete cationic agglomerate component composed of at least one water-soluble or partially water-soluble calcium salt and a first inert solid carrier, and (B) a discrete anionic agglomerate component composed of at least one water-soluble orthophosphate salt and a second inert solid carrier. The agglomerate nature of the cationic and anionic components keeps these components separate from one another during storage of the product but allows the cationic and anionic salts to be simultaneously released from the product upon mixing of the product with water and/or saliva to form a mixed aqueous solution such that the solution contains both calcium cations released from the calcium salt and orthophosphate anions released by the orthophosphate salt.

This application is a continuation application of U.S. Ser. No.09/322,918, filed Jun. 1, 1999 now abandoned.

BACKGROUND OF THE INVENTION

This invention is related to oral products capable of remineralizingsubsurface dental lesions and/or mineralizing exposed dentinal tubules.More particularly, this invention is related to oral products capable ofremineralizing subsurface dental lesions and/or mineralizing exposeddentinal tubules, wherein the oral products contain discrete cationicand anionic phases which do not react with one another prior to use ofthe product. This invention is further related to methods of using theoral products of this invention to remineralize subsurface dentallesions and/or mineralize exposed dentinal tubules.

The primary component of the enamel and dentin in teeth is calciumphosphate in the form of calcium hydroxyapatite. This material is highlyinsoluble at normal oral pHs but tends to dissolve in acidic media.Thus, when teeth are exposed to acids, e.g., acids generated during thebacteria-induced glycolysis of sugar in the oral cavity, lesions (i.e.,demineralized areas) can form below the surface of intact enamel. Dentalcaries, the leading cause of tooth damage in humans, usually begins withthese subsurface lesions, which are formed before a cavity is evendetectable. If unchecked, the surface enamel above a subsurface lesionwill eventually collapse, leading to cavitation and subsequent loss oftooth structure.

Subsurface remineralization can arrest and repair the carious lesionsbefore any permanent structural damage to the tooth occurs. Unlikesurface remineralization processes, which deposit calcium phosphate ontothe tooth surface, subsurface remineralization processes precipitatecalcium phosphate in the subsurface enamel where demineralizationinitially occurs.

Saliva is supersaturated with calcium and orthophosphate ions and,therefore, can help protect teeth against demineralization andremineralize teeth which have become demineralized. However, becausesaliva contains only modest levels of these ions, saliva-promotedremineralization tends to be slow.

The remineralization process can be speeded up by increasing theconcentrations of dissolved calcium and orthophosphate ions in the oralcavity. However, this is not easy to do because, at the pH levels in theoral cavity, calcium and orthophosphate ions have a strong affinity forone another and tend to rapidly precipitate calcium phosphate. If suchprecipitation occurs too soon, subsurface remineralization, whichrequires that the calcium and orthophosphate ions remain soluble for aperiod of time sufficient to permit their diffusion into thedemineralized subsurface of the dental enamel, will be reduced orprevented.

Thus, to achieve subsurface remineralization, precipitation of thecalcium phosphate must be delayed until sufficient levels of the calciumand orthophosphate ions have reached the subsurface of the tooth.

A number of remineralizing products and methods have been developedwhich are designed at least in part to prevent premature reactionbetween calcium and orthophosphate ions used in such product or method.Reference is made, for example, to U.S. Pat. Nos. 4,083,955; 4,080,440;4,606,912; 4,610,873; 4,397,837; 4,348,381; 4,177,258; 4,183,915;4,460,565; 5,037,639; 5,268,167; 5,427,768; 5,437,857; and 5,460,803.Reference is also made to commonly assigned U.S. Pat. Nos. 5,571,502;5,603,922; 5,605,675; 5,614,175; 5,645,853; 5,817,296; 5,833,957;5,858,333; 5,866,102; and 5,895,641.

U.S. Pat. No. 4,083,955 (Grabenstetter et al.) discloses a method forremineralizing subsurface dental enamel, wherein a calcium salt solutionand a phosphate salt solution are sequentially applied to dental enamelto effect subsurface remineralization thereof. The delivery system forthe calcium and phosphate salt solutions can be in the form of twoseparate delivery vehicles, each containing one component, or in theform of a single delivery vehicle which contains both components butreleases them sequentially. Examples of two-vehicle systems includemouthwash—mouthwash, toothpaste—toothpaste, candy drop—candy drop,nutritional substance—nutritional substance, andtoothpowder—toothpowder. Examples of one-vehicle systems include atoothpaste wherein one ingredient is encapsulated for delayed release, atwo-compartment bottle, a lozenge with a laminated structure so thatfirst one ionic ingredient is released and then the other, a chewing gummade so that one ingredient is released before the other, and anutritional substance in which one ingredient is released before theother.

U.S. Pat. No. 4,080,440 (DiGiulio et al.) discloses a method and atwo-part product for remineralizing subsurface lesions in dental enamel,wherein the product contains a cationic part composed of a water-solublecalcium salt and an anionic part composed of a water-soluble phosphatesalt. Remineralization is carried out by mixing a solution containingthe cationic part with a solution containing the anionic part to form ametastable solution which is then promptly applied to the teeth.DiGiulio et al. teaches that the cationic and anionic parts are storedseparately in the product to avoid premature precipitation of calciumphosphate. The product, examples of which include two-part mouthwashesand two-part toothpastes, may be in the form of a kit composed ofseparately packaged solutions of the respective cations and anions. As atwo-part toothpaste, the product may be packaged in a codispensingtoothpaste tube.

U.S. Pat. Nos. 4,606,912 and 4,610,873 (both to Rudy et al.) are eachdirected to an aqueous mouthwash solution which is maintainable as aone-bottle solution and capable of remineralizing caries lesions inteeth. The solution is made by forming an aqueous solution containing asource of calcium ions and a chelating agent for calcium ions, causingthe chelation of at least 50% of the calcium ions, and subsequentlyadding a source of phosphate ions to the aqueous solution. The Rudy etal. patents teach that by bringing about the chelation of at least 50%of the calcium ions, the precipitation of calcium phosphate from thesolution is avoided.

U.S. Pat. Nos. 4,177,258, 4,183,915 and 4,348,381 (all to Gaffar et al.)are each directed to stable, one-part aqueous compositions capable ofremineralizing carious lesions in dental enamel and composed of asolution of water having dissolved therein a source of calcium ions anda source of phosphate ions, a fluoride compound and an antinucleatingagent. The Gaffar et al. patents teach that the antinucleating agentprevents spontaneous precipitation of calcium phosphate on the enamelsurfaces and thereby permits diffusion of the remineralizing componentsto the subsurface lesions. The Gaffar et al. patents further teach thatthe aqueous remineralizing composition is suitably prepared as a dentalmouthrinse and also can be incorporated into other dentifricecompositions such as a dental cream or gel, mouth spray, troche,chewable tablet, lozenge and the like.

U.S. Pat. No. 4,460,565 (Weststrate et al.) discloses an anticariogenicremineralizing dentifrice containing two or more fluorine compounds, atleast one water-soluble phosphate salt and at least one compoundproviding calcium ions. Examples of such dentifrices includetoothpastes, prophylactic pastes, tooth polishes, mouth waters,application liquids, gels, and specific chewing gums. Weststrate et al.teaches that the specific calcium complexes used as the source ofcalcium ions therein are capable of retaining the calcium in an activeform in dentifrices without deactivating the phosphate and fluorideions.

U.S. Pat. Nos. 5,037,639; 5,268,167; 5,437,857; 5,427,768; and 5,460,803(all to Tung) involve the use of amorphous calcium compounds such asamorphous calcium phosphate (ACP), amorphous calcium phosphate fluoride(ACPF) and amorphous calcium carbonate phosphate (ACCP) for use inremineralizing teeth. These amorphous compounds or solutions which formthe amorphous compounds when applied either onto or into dental tissueprevent and/or repair dental weaknesses such as dental caries, exposedroots and dentin sensitivity. Remineralization is accomplished bybringing the amorphous compound into contact with the dental tissue.This can be done directly, i.e., putting an amorphous compound directlyon the tooth, or indirectly through a carrier, i.e., incorporating theamorphous compound in a carrier such as a gel, a chewing gum, or atoothpaste and applying the carrier to the dental tissue. Once contactis established with the tooth, the amorphous calcium phosphate compoundswill recrystallize to the less soluble apatite form in the lesion andreform the tooth. However, under conditions where amorphous calciumphosphate compounds are stable, the quantity of calcium and phosphatereleased is relatively low and, therefore, remineralization is slowerthan desirable. The Tung patents also teach the use of two-partsolutions wherein a first part contains phosphate salt(s) and a secondpart contains calcium salt(s), wherein either the first part or thesecond part further contains carbonate salt(s). In addition, the Tungpatents teach solutions formed by dissolving in water a solid powdercontaining calcium salt(s), phosphate salt(s), and carbonate salt(s).These solutions are then applied to dental tissue. The Tung patentsfurther teach the use of non-carbonated solid powders containingmixtures of calcium salts and phosphate salts which can be applieddirectly to the tooth or dispersed in gel, chewing gum, or othernon-aqueous mediums such as toothpaste which is placed in contact withthe tooth.

U.S. Pat. Nos. 5,603,922, 5,817,296, 5,833,957 and 5,858,333 (all toWinston et al.) each disclose one-part and/or two-part products andmethods of using same to remineralize subsurface lesions. The one-partand two-part products contain at least one water-soluble calcium salt,at least one water-soluble divalent metal salt wherein the divalentmetal is other than calcium and at least one water-soluble phosphatesalt. In the two-part products, the calcium and divalent metal salts aredisposed in a first discrete component, and the phosphate salt(s) isdisposed in a second discrete component.

U.S. Pat. Nos. 5,605,675 and 5,895,641 to Usen et al. disclose atwo-part product and method of using same for remineralizing dentalenamel, wherein the product contains a first discrete componentcontaining at least one water-soluble calcium salt and a second discretecomponent containing at least one water-soluble phosphate salt and atleast one water-soluble fluoride salt.

U.S. Pat. No. 5,645,853 to Winston et al. is directed to a chewing gumproduct and method of using same for remineralizing subsurface lesionsin teeth, wherein the product contains a water-soluble cationic portioncomposed of at least one water-soluble calcium salt and at least onewater-soluble, non-toxic divalent metal salt wherein the divalent metalis other than calcium; a water-soluble anionic portion containing atleast one water-soluble phosphate salt; and a gum base.

U.S. Pat. Nos. 5,571,502, 5,614,175 and 5,866,102 (all to Winston etal.) are each directed to one-part, non-aqueous products and methods ofusing same for remineralizing subsurface lesions, wherein the productscontain at least one water-soluble calcium salt; at least onewater-soluble phosphate salt; either a stabilizer or a hydrophilic,non-aqueous, water-soluble vehicle; and, optionally, at least onewater-soluble fluoride salt. When the components are mixed with water orsaliva to form an aqueous mixed solution, the solution has a pH of fromabout 4.5 to about 10.0.

Although the aforementioned patents disclose various ways of keeping thecalcium and phosphate ions separate from one another during storage ofthe product, it would be desirable to provide an easier and lessexpensive way of keeping the calcium and phosphate ions separate beforeuse.

Particularly useful oral products for deliveringremineralizing/mineralizing components to the teeth are chewing gumproducts. This is because the inherent nature of chewing gums allowsprolonged contact with the teeth and further because the gum base canprovide sustained release of the remineralizing/mineralizing components,thereby minimizing the amount of such components that must be used.

Several of the aforementioned patents disclose the use ofremineralizing/mineralizing chewing gum products and other solid oralproducts. Non-limiting examples of other patents which teach the use ofchewing gums or other solid oral products to deliver active componentsto teeth include U.S. Pat. Nos. 4,233,288; 4,828,845; 4,405,600;5,204,115; 4,153,732; 3,892,843; 4,906,455; 4,902,498; 5,496,558; and5,380,530.

Thus, it would be desirable to provide a chewing gum product, as well asother solid oral products, which contain remineralizing-mineralizingcationic and anionic salts, wherein the chewing gum product usesrelatively inexpensive and easy means for keeping the salts separatefrom another during storage of the product.

Accordingly, a primary object of this invention is to provide an oralproduct capable of remineralizing subsurface dental lesions and capableof mineralizing exposed dentinal tubules and composed of water-solublecalcium and phosphate salts, wherein the product uses relativelyinexpensive and easy means to keep the salts separate from one anotherin the product.

A further object of this invention is to provide an oral product havingthe aforementioned characteristics, wherein the product is a solid oralproduct such as, e.g., a chewing gum product, a lozenge, a candyproduct, an edible foodstuff, a toothpowder, and the like.

A still further object of this invention is to provide a method ofremineralizing subsurface dental lesions and/or mineralizing exposeddentinal tubules, using an oral product having the aforementionedcharacteristics.

These and other objects which are achieved according to the presentinvention can be discerned from the following description.

SUMMARY OF THE INVENTION

In the present invention, remineralizing-mineralizing cationic andanionic salts are kept from reacting with one another prior to use ofthe oral product by disposing these salts as separate cationic andanionic agglomerates in the product. The agglomerated nature of thecationic and anionic salts allows these salts to be effectivelyseparated from one another during storage of the product but also allowsthese salts to be simultaneously released from the product upon contactwith water, such as, e.g., by chewing, sucking or eating.

Thus, in one aspect thereof, the present invention provides a solid oralproduct capable of remineralizing subsurface dental lesions and capableof mineralizing exposed dentinal tubules, containing:

(A) a discrete cationic agglomerate component composed of aremineralizing-mineralizing amount of at least one water-soluble orpartially water-soluble calcium salt and a first inert solid carrier,and

(B) a discrete anionic agglomerate component composed of aremineralizing-mineralizing amount of at least one water-solubleorthophosphate salt and a second inert solid carrier;

wherein components (A) and (B) have a pH in water such that a mixedaqueous solution formed by mixing components (A) and (B) with waterand/or saliva has a pH of from about 4.5 to about 10.0;

further wherein the cationic and anionic agglomerate components aresimultaneously releasable from the product upon mixing of the productwith water and/or saliva to form the mixed aqueous solution such thatthe mixed aqueous solution contains calcium cations released from thecalcium salt and orthophosphate anions released by the orthophosphatesalt.

The solid oral product of this invention may be in the form of a chewinggum, a lozenge, a candy, an edible foodstuff, a tablet, a toothpowder,and the like.

Another aspect of the present invention is directed to a method of usingthe solid oral product of this invention to remineralize at least onesubsurface dental lesion and/or mineralize at least one exposed dentinaltubule in at least one tooth. Such method involves the steps of:

(1) providing the oral product of this invention;

(2) contacting the product with water and/or saliva so as to form amixed aqueous solution having a pH of from about 4.5 to about 10.0 andcontaining calcium cations released by the calcium salt andorthophosphate ions released by the orthophosphate salt; and

(3) contacting the at least one tooth with the mixed aqueous solutionfor a period of time sufficient to allow a remineralizing/mineralizingamount of the calcium anions and a remineralizing/mineralizing amount ofthe orthophosphate anions to diffuse through the tooth to a subsurfacethereof, wherein the diffused calcium cations and the diffusedorthophosphate anions react together to form calcium hydroxyapatite ontothe subsurface lesion and/or onto the exposed dentinal tubule, therebyremineralizing the lesion and/or mineralizing the exposed dentinaltubule.

If the product is a chewing gum, step (2) of the method of thisinvention involves chewing the product to release the calcium andorthophosphate salts. If the product is a lozenge, step (2) involvessucking the product. If the product is an edible foodstuff, step (2)involves eating the product.

DETAILED DESCRIPTION OF THE INVENTION

As stated above, the present invention is directed to solid oralproducts and methods of using same to remineralize subsurface dentallesions and/or to mineralize exposed dentinal tubules.

As used herein, the term “solid oral product” refers to a product whichcan be sucked, chewed or eaten. Non-limiting examples of such productsinclude chewing gums, lozenges, candies, food products, dragees, bonbons, toothpowders, and the like.

The oral product of this invention contains a discrete cationicagglomerate component and a discrete anionic agglomerate component. Thediscrete cationic agglomerate component contains aremineralizing-mineralizing amount of at least one water-soluble orpartially water-soluble calcium salt and may contain one or morenon-toxic, water-soluble salts of a divalent metal other than calcium.The discrete anionic agglomerate component contains aremineralizing-mineralizing amount of at least one water-solubleorthophosphate salt and, optionally, at least one water-soluble fluoridesalt.

With respect to the amounts of the calcium and orthophosphate salts, theterm “remineralizing-mineralizing amount” means that amount which issufficient to effect substantial remineralization of subsurface lesionsin teeth and/or to effect substantial mineralization of exposed dentinaltubules.

As used herein with respect to the partially water-soluble calciumsalt(s), the term “partially water-soluble” refers to a calcium salthaving a solubility which is greater than that of dicalcium phosphatedihydrate in an aqueous solution having a pH of about 7.0 and atemperature of about 25° C. but which is less than that solubility whichwould release more than about 1400 ppm of calcium cations in suchaqueous solution. In an aqueous solution having a pH of about 7.0 at atemperature of about 25° C., dicalcium phosphate dihydrate can releaseup to about 40 ppm of calcium cations by weight of the aqueous solution.Thus, partially water-soluble calcium salts useful in the oral productof this invention include calcium salts having a solubility in watersuch that the salt is capable of releasing more than about 40 ppm but nomore than about 1400 ppm, preferably from about 100 ppm to no more thanabout 1400 ppm, of calcium cations by weight of an aqueous solutionhaving a pH of about 7.0 at a temperature of about 25° C. As used hereinwith respect to the water-soluble calcium salt(s), water-solubleorthophosphate salt(s), water-soluble non-calcium divalent metal salt(s)and water-soluble fluoride salt(s), the term “water-soluble” refers to asolubility in water such that the salt is capable of releasing at leastabout 1400 ppm by weight of ions into an aqueous solution having atemperature of about 25° C. and a pH of about 7.0.

As will be discussed in greater detail hereinbelow, the oral products ofthis invention are made by forming separate agglomerates of the calciumand orthophosphate salts in combination with other dry, inert materialsand carriers such as, e.g., sorbitol, mannitol, silicas, insolublecalcium phosphates, and the like. The agglomerate composed of thecalcium salt(s) may further contain the non-calcium divalent metalsalt(s), while the agglomerate containing the orthophosphate salt(s) mayalso contain the water-soluble fluoride salt(s). The agglomeratecontaining the calcium salt(s) is referred to herein as the “cationicagglomerate” or the “cationic agglomerate component”, while theagglomerate containing the orthophosphate salt(s) is referred to hereinas the “anionic agglomerate” or the “anionic agglomerate component”.

The cationic and anionic agglomerates are then incorporated into a basicsolid oral product, e.g., chewing gum, lozenge, and the like, to formthe remineralizing/mineralizing final solid oral product of thisinvention. As used herein, the term “basic solid oral product” refers toa solid oral product to which the agglomerates of this invention havenot been added.

The cationic and anionic agglomerates used in the present invention maybe made by several different methods including, e.g., direct compression(i.e., dry agglomeration) methods, wet granulation methods, andabsorption methods (involving absorption onto inert substances).

In direct compression methods, the calcium salt is intimately mixed witha first inert carrier, and the orthophosphate salt is intimately mixedwith a second inert carrier. Each mixture is then compressed into dryflakes, tablets or agglomerates using, e.g., a tablet press or aChilsonator. The resulting solids are then ground to the desiredagglomerate size and added to a basic solid oral product (which has beenformed according to known methods) to form the final product of thisinvention.

The most preferred inert carriers for use in direct compressionprocesses are sorbitol, mannitol and xylitol.

In wet granulation processes, the calcium salt and a first inert carrierare placed in a mixer/agglomerator, and the orthophosphate salt and asecond inert carrier are placed in a separate mixer/agglomerator. Thetwo sets of materials then undergo mixing and agglomeration in thepresence of water or other liquid. The powdered materials beingagglomerated or the liquid being added preferably contains a binder tohold the agglomerated material together after drying. Suitable bindersinclude, for example, PVP, polyvinyl acetate (PVA) orcarboxymethylcellulose (CMC). The calcium-containing product and thephosphate-containing product are then dried and ground to the desiredparticle size. The particles are then added to a basic solid oralproduct to form the final product.

For wet agglomeration processes, the preferred inert carriers areinsoluble materials such as, e.g., silicas or insoluble calciumphosphates. Non-limiting examples of suitable insoluble calciumphosphates include dicalcium phosphate dihydrate, anhydrous dicalciumphosphate, tricalcium phosphate and calcium hydroxyapatite.

Another method for making the agglomerates used in the present inventioninvolves absorbing the calcium salt (and non-calcium divalent metalsalt, if present) and the orthophosphate salt (and the fluoride salt, ifpresent) onto separate inert substances. For example, the calcium andorthophosphate salts can be dissolved separately in water and theresulting solutions each added, with mixing, to an absorbent material ofan appropriate particle size. If desired, PVP, CMC or other polymer canbe included in the respective solutions to form a soluble film aroundthe particles or to promote agglomeration of the absorbing particles.The materials are then dried and added to a basic solid oral product toform the final product.

The agglomerated particles used in the present invention preferably havea particle size of from about 100 to about 2000 microns. For smooth oralproducts, the particle sizes preferably range from about 400 to about840 microns. For crunchy oral products, the particle sizes preferablyrange from about 840 to about 2000 microns.

As stated above, the cationic agglomerate component used in thisinvention contains at least one water-soluble or partially water-solublecalcium salt, and the anionic agglomerate component contains at leastone water-soluble orthophosphate salt.

Non-limiting examples of partially water-soluble calcium salts suitablefor use in this invention include calcium sulfate, anhydrous calciumsulfate, calcium sulfate hemihydrate, calcium sulfate dihydrate, calciummalate, calcium tartrate, calcium malonate, calcium succinate, andmixtures of the foregoing. Calcium sulfate is preferred.

Partially water-soluble calcium salts can be prepared in situ, forexample, by preparing mixtures of an acid such as, e.g., tartaric acid,and a water-soluble calcium salt such as, e.g., calcium nitrate, andadjusting the pH as needed.

Non-limiting examples of water-soluble calcium salts useful in theproduct of this invention include, for example, calcium chloride,calcium lactate, calcium nitrate, calcium acetate, and calciumgluconate. Calcium lactate is preferred.

Mixtures of water-soluble and partially water-soluble calcium salts maybe used in the oral product of this invention.

Suitable water-soluble inorganic orthophosphate salts for use in thepresent invention include, for example, alkali salts and ammonium saltsof orthophosphoric acid, such as, e.g., potassium, sodium or ammoniumorthophosphate; monopotassium orthophosphate; dipotassiumorthophosphate; tripotassium orthophosphate; monosodium orthophosphate;disodium orthophosphate and trisodium orthophosphate.

As stated previously herein, the cationic agglomerate component mayfurther contain one or more non-toxic, divalent metal salts other thancalcium salt. Such salts release divalent metal cations which help tostabilize the mixed aqueous solution against rapid precipitation of thecalcium cations and the phosphate and fluoride anions (if present). Theremineralizing cations and anions can then diffuse through the toothsurface to the demineralized subsurface lesion(s) and/or the exposeddentin tubule where the diffused cations and anions then react to forman insoluble precipitate which is bound to the tooth. As a result, whenan effective amount of the divalent metal cations is used, thesubsurface lesion is more effectively remineralized or desensitizedand/or the exposed dentin tubule is more effectively mineralized.

The divalent metal salt(s) which can be used in the products of thepresent invention may be any water-soluble, non-toxic divalent metalcompound which will stabilize the calcium, phosphate and fluoride ionsso that these ions do not rapidly or prematurely precipitate beforediffusing into the teeth. In practice, however, it has been found thatat least one member selected from the group consisting of magnesium,strontium, tin, and zinc, with magnesium being preferred, is the mosteffective divalent metal in stabilizing the system.

Suitable magnesium compounds include, for example, magnesium acetate,magnesium ammonium sulfate, magnesium benzoate, magnesium bromide,magnesium borate, magnesium citrate, magnesium chloride, magnesiumgluconate, magnesium glycerophosphate, magnesium hydroxide, magnesiumiodide, magnesium oxide, magnesium propionate, magnesium D-lactate,magnesium DL-lactate, magnesium orthophosphate, magnesiumphenolsulfonate, magnesium pyrophosphate, magnesium sulfate, magnesiumnitrate, and magnesium tartrate. Preferred magnesium compounds aremagnesium chloride, magnesium acetate and magnesium oxide.

Suitable strontium compounds include, for example, strontium acetate,strontium ammonium sulfate, strontium benzoate, strontium bromide,strontium borate, strontium caprylate, strontium carbonate, strontiumcitrate, strontium chloride, strontium gluconate, strontiumglycerophosphate, strontium hydroxide, strontium iodide, strontiumoxide, strontium propionate, strontium D-lactate, strontium DL-lactate,strontium pyrophosphate, strontium sulfate, strontium nitrate, andstrontium tartrate. Preferred strontium compounds are strontium acetate,strontium chloride, strontium nitrate.

Suitable tin compounds include, for example, stannous acetate, stannousammonium sulfate, stannous benzoate, stannous bromide, stannous borate,stannous carbonate, stannous citrate, stannous chloride, stannousgluconate, stannous glycerophosphate, stannous hydroxide, stannousiodide, stannous oxide, stannous propionate, stannous D-lactate,stannous DL-lactate, stannous orthophosphate, stannous pyrophosphate,stannous sulfate, stannous nitrate, and stannous tartrate. A preferredtin compound is stannous chloride.

Suitable zinc compounds include, for example, zinc acetate, zincammonium sulfate, zinc benzoate, zinc bromide, zinc borate, zinccitrate, zinc chloride, zinc gluconate, zinc glycerophosphate, zinchydroxide, zinc iodide, zinc oxide, zinc propionate, zinc D-lactate,zinc DL-lactate, zinc pyrophosphate, zinc sulfate, zinc nitrate, andzinc tartrate. Preferred zinc compounds are zinc acetate, zinc chloride,zinc sulfate, and zinc nitrate.

In addition to the water-soluble orthophosphate salt(s), the anionicagglomerate component used in the present invention may further containat least one water-soluble fluoride salt. Suitable water-solublefluoride salts for use in the present invention include the alkali metalor ammonium fluorides such as sodium, potassium, lithium or ammoniumfluoride; tin fluoride; indium fluoride; zirconium fluoride; copperfluoride; nickel fluoride; palladium fluoride; fluorozirconates such assodium, potassium or ammonium fluorozirconate or tin fluorozirconate;fluorosilicates; fluoroborates; and fluorostannites. Although notpreferred, fluorophosphates, such as sodium fluorophosphate, potassiumfluorophosphate and ammonium fluorophosphate, are also suitable for usein the present invention. In addition, organic fluorides, such as theknown amine fluorides, can also be used in the oral products of thisinvention.

Sodium fluoride is the preferred fluoride salt for use in the presentinvention.

In preferred embodiments of the present invention, the respectiveremineralizing/mineralizing amounts of the cationic and anionicagglomerate components are such as to provide a mixed aqueous solutioncomposed of these salts with from about 100 ppm to about 15,000 ppm ofdissolved calcium ions and from about 100 ppm to about 15,000 ppm ofdissolved orthophosphate ions.

If a non-calcium divalent metal salt is used in the cationic agglomeratecomponent, the amount of such salt used should be such as to provide themixed aqueous solution with at least about 10 ppm, more preferably atleast about 100 ppm, and most preferably from about 100 ppm to about20,000 ppm of divalent metal cations.

To avoid fluorosis and other toxic effects, it is undesirable to ingestan average of more than about 0.2 mg of fluoride from all sources allday. Therefore, the concentration of fluoride provided in products ofthe invention should be appropriately limited. The concentration offluoride ions in a chewing gum, tablet, or lozenge should be no morethan about 100 ppm, preferably no more than 20 ppm, most preferably inthe range of from 0.5 to 10 ppm. In edible foods, the purposefuladdition of fluoride should be avoided.

The products of this invention preferably contain from about 0.05% toabout 15.0% by weight, more preferably from about 0.10% to about 10.0%by weight, of the calcium salt(s), and from about 0.05% to about 15.0%by weight, more preferably from about 0.10% to about 10.0% by weight, ofthe orthophosphate salt(s). The product may further contain at least0.0001%, preferably from about 0.001% to about 2.0%, and more preferablyfrom about 0.01% to about 1.0%, by weight of the divalent metal salt(s).

The products of this invention contain a molar ratio of the calciumsalt(s) to the orthophosphate salt(s) of preferably from about 0.01:1 toabout 100:1. Most preferably, the concentration of the calcium salt(s)and the concentration of the orthophosphate salt(s) are preferablyessentially the same in the products of this invention. Theconcentration of the calcium salt(s) may exceed the solubility of suchsalt, whereas the concentration of the orthophosphate salt(s) is usuallyas high or even higher than the solubility thereof.

The cationic and anionic agglomerate components used in the presentinvention have a pH in water such that a mixed aqueous solution formedby mixing these components with water and/or saliva has a pH of fromabout 4.5 to about 10.0, preferably from about 5.0 to about 7.0, morepreferably from about 5.0 to about 5.75. At a pH within such range,enough of the calcium ions, orthophosphate ions and, if present,non-calcium divalent metal ions and fluoride ions in the mixed aqueoussolution remain soluble for the period of time required to allowsufficient amounts of the ions to diffuse through the tooth surface soas to substantially remineralize the subsurface lesions and/orsubstantially mineralize the exposed tubules of the dental enamel. Ifthe mixed aqueous solution has a pH below about 3, demineralization willoccur rapidly because the concentration of calcium and phosphate insaliva is likely to be significantly below saturation. A pH below about2.5 is undesirable from a safety standpoint.

The pH of the mixed aqueous solution may be adjusted to the desired pHby methods well known in the art. The pH may be lowered by the additionof any acid which is safe for use in the oral cavity and which yieldsthe desired pH at the amount employed. Examples of suitable acidsinclude acetic acid, phosphoric acid, citric acid, malic acid, gluconicacid and succinic acid. Alternatively, acidic phosphate salts can beused to produce an acidic pH and alkaline phosphate salts can be used toproduce an alkaline pH.

As stated previously herein, the solid oral products of this inventionare prepared by incorporating the cationic and anionic agglomeratecomponents into a basic solid oral product, e.g., chewing gum, lozenge,and the like. An alternative way of preparing the product of thisinvention is to provide for two separate solid oral products (e.g.,chewing gums or lozenges) which are then broken up into pieces. Thepieces are then homogeneously mixed and compressed together to produce asingle solid oral product (e.g., a single gum or lozenge) composed ofseparate zones containing the calcium and phosphate salts. For example,a lozenge can be prepared from two lozenges wherein one lozenge containsthe calcium-containing composition and the second lozenge contains thephosphate-containing composition. The lozenges are then grinded intoparticles which are then homogeneously mixed and compressed into asingle lozenge containing separate zones of calcium and orthophosphatesalts.

The present invention further provides a method of remineralizingsubsurface dental lesions and/or mineralizing exposed dentinal tubulesusing the oral product of this invention. The method of this inventioninvolves the steps of:

(1) providing the oral product of this invention;

(2) causing the oral product to be mixed with water and/or saliva in theoral cavity so as to form a mixed aqueous solution having a pH of fromabout 4.5 to about 10.0 and containing calcium ions released by thecalcium salt and orthophosphate ions released by the orthophosphatesalt; and

(3) promptly after formation of the mixed aqueous solution, applying thesolution to the tooth for a period of time sufficient to allow aremineralizing amount of the calcium ions and a remineralizing amount ofthe orthophosphate ions to diffuse through the tooth to a subsurfacearea thereof, the diffused calcium ions and the diffused orthophosphateions reacting at the subsurface area to form an insoluble calciumphosphate precipitate which is bound to the tooth, therebyremineralizing the subsurface lesion and/or mineralizing the exposeddentinal tubule.

The length of time in which the tooth is treated with the mixed aqueoussolution is important to the present invention. The period of treatmentneeds to be long enough to allow diffusion of the ions through the toothsurface to the demineralized subsurface lesion(s) and/or exposed dentintubule(s). Such period of treatment is preferably at least about 2minutes, more preferably at least about 5 minutes, and most preferablyat least about 15 minutes.

As stated previously herein, the ions which have diffused through thetooth surface form an insoluble precipitate on the demineralizedsubsurface lesion(s) and/or on the exposed dentin tubule(s). Althoughmany precipitates are within the broad scope of this invention, it ispreferred that the precipitate render the remineralized subsurfaceand/or mineralized dentin of the tooth treated in accordance with thisinvention more resistant to demineralization than was the originalenamel. Thus, the preferred precipitate is one which is less solublethan the original enamel. Tooth enamel primarily contains a slightlycarbonated apatite. If the precipitating species is not carbonated, theprecipitate will be somewhat less soluble than the original enamel.Therefore, when fluoride anions are not present, it is desirable thatconditions be present which favor the precipitation of unsubstitutedhydroxyapatite. Thus, for example, it is desirable to avoid the additionof carbonates or bicarbonates to non-fluoride compositions. On the otherhand, if fluoride salts are used in the products of this invention, theapatite will incorporate fluoride anions, thus rendering the precipitatemore resistant to demineralization than was the original enamel.However, even when fluoride anions are not directly added to theremineralizing/mineralizing mixed aqueous composition used in thepresent invention, it has been found that the teeth treated with suchcomposition will absorb more fluoride when subsequently treated with afluoride-containing product (e.g., a fluoride toothpaste) than teethwhich had not been pretreated with such composition.

Thus, the precipitate formed in the present invention is preferably acalcium phosphate or a hydroxyapatite.

Therefore, use of the products of this invention not only remineralizesthe demineralized enamel and/or mineralize the exposed dentin tubulesbut also renders such remineralized enamel and/or mineralized dentintubule more resistant to subsequent demineralization than was theoriginal enamel or tubule.

The mixed aqueous solution formed from the products of this inventionand the insoluble precipitate formed from the mixed aqueous solutionmust both have acceptable levels of toxicity. In other words, theparticular ions, in the amounts used in the remineralization and/ormineralization process, must be non-toxic. Furthermore, such solutionand precipitate should be otherwise compatible in the oral environment.

As mentioned previously herein, the solid product of this invention maybe in the form of a chewing gum, a lozenge, a candy, an edible foodproduct, a tablet, a toothpowder, and the like. In preferredembodiments, the solid product of this invention is a chewing gum orlozenge, more preferably a chewing gum.

Chewing gums are the preferred vehicles for delivering the cationic andanionic components of the present invention because the inherent natureof chewing gums allows prolonged contact with the teeth and, further,because the gum base can provide sustained release of the anionic andcationic components of the products of this invention, thus minimizingthe amount of the anionic and cationic components that must be used.

Chewing gum products within the scope of this invention may be any of avariety of different chewing gums, bubble gums, dragees, and the like,including low or high moisture, sugar or sugarless, wax-containing orwax-free, low calorie (via high base or low calorie bulking agents),and/or may contain other dental health agents.

Chewing gum generally consists of a water-insoluble gum base, awater-soluble portion and flavors. The water-soluble portion dissipateswith a portion of the flavor over a period of time during chewing. Thegum base portion is retained in the mouth throughout the chew.

The insoluble gum base generally contains elastomers, resins, fats andoils, softeners, and inorganic fillers. The gum base may or may notinclude wax. The insoluble gum base can constitute from about 5% toabout 95%, preferably from about 10% to about 50%, more preferably fromabout 20% to about 35%, by weight of the chewing gum.

In one embodiment, the chewing gum base which can be used in the presentinvention contains from about 20% to about 60% by weight of a syntheticelastomer, from 0% to about 30% by weight of a natural elastomer, fromabout 5% to about 55% by weight of an elastomer plasticizer, from about4% to about 35% by weight of a filler, from about 5% to about 35% byweight of a softener, and, optionally, minor amounts (about 1% by weightor less) of miscellaneous ingredients such as colorants, antioxidants,and the like.

Synthetic elastomers suitable for use herein include but are not limitedto polyisobutylene with GPC weight average molecular weight of fromabout 10,000 to about 95,000, preferably from about 50,000 to about80,000; isobutylene-isoprene copolymer (butyl elastomer);styrene-butadiene copolymers having styrene-butadiene ratios of fromabout 1:3 to about 3:1, preferably from about 1:1 to about 1:3;polyvinyl acetate having a GPC weight average molecular weight of fromabout 2000 to about 90,000, preferably from about 10,000 to about65,000; polyisoprene; polyethylene; vinyl acetate-vinyl lauratecopolymer having a vinyl lauryl content of from about 5% to about 50% byweight, preferably from about 10% to about 45% by weight, of thecopolymer, and combinations thereof.

Non-limiting examples of suitable natural elastomers include naturalrubber such as smoked or liquid latex and guayule as well as naturalgums such as jelutong, lechi caspi, perillo, sorva, massaranduba balata,massaranduba chocolate, nispero, rosindinha, chicle, gutta hang kang,and combinations thereof. Preferred natural elastomers include jelutong,chicle, sorva, and massaranduba balata.

The preferred concentrations of the synthetic elastomer and the naturalelastomer will vary depending on whether the chewing gum in which thebase is used is adhesive or conventional, bubble gum or regular gum, asdiscussed below.

Non-limiting examples of suitable elastomer plasticizers include naturalrosin esters such as glycerol esters of partially hydrogenated rosin,glycerol esters polymerized rosin, glycerol esters of partiallydimerized rosin, glycerol esters of rosin, penta-erythritol esters ofpartially hydrogenated rosin, methyl and partially hydrogenated methylesters of rosin, pentaerythritol esters of rosin; synthetics such asterpene resins derived from alpha-pinene, beta-pinene, and/ord-limonene; and any suitable combinations of the foregoing. Thepreferred elastomers will also vary depending on the specificapplication, and on the type of elastomer which is used.

Non-limiting examples of suitable fillers/texturizers include magnesiumand calcium carbonate; ground limestone; silicate types such asmagnesium and aluminum silicate; clay; alumina; talc; titanium oxide;mono-, di- and tri-calcium phosphate; cellulose polymers, such as wood;and combinations thereof.

Non-limiting examples of suitable softeners/emulsifiers include tallow;hydrogenated tallow; hydrogenated and partially hydrogenated vegetableoils; cocoa butter; glycerol monostearate; glycerol triacetate;lecithin; mono-, di-, and triglycerides; acetylated monoglycerides;fatty acids such as stearic acid, palmitic acid, oleic acid and linoleicacid; and combinations thereof.

Suitable colorants and whiteners include, e.g., FD&C-type dyes andlakes, fruit and vegetable extracts, titanium dioxide and combinationsthereof.

The base may or may not include wax.

In addition to a water-insoluble gum base portion, a typical chewing gumproduct includes a water-soluble bulk portion and one or more flavoringagents. The water-soluble portion can include, e.g., bulk sweeteners,high intensity sweeteners, flavoring agents, softeners, emulsifiers,colors, acidulants, fillers, antioxidants, and other components thatprovide desired attributes.

Softeners are added to chewing gum products to optimize the chewabilityand mouth feel of the gum. The softeners, which are also known asplasticizers and plasticizing agents, generally constitute from about0.5% to about 15% by weight of the chewing gum. The softeners mayinclude, e.g., glycerin, lecithin, and combinations thereof. Aqueoussweetener solutions such as those containing sorbitol, hydrogenatedstarch hydrolysates, corn syrup and combinations thereof, may also beused as softeners and binding agents in chewing gum products.

Bulk sweeteners include both sugar and sugarless components. The bulksweetener(s) preferably constitutes from about 5% to about 95% byweight, more preferably from about 20% to about 80% by weight, and mostpreferably from about 30% to about 60% by weight, of the chewing gum.

Sugar sweeteners generally include saccharide-containing components suchas, e.g., sucrose, dextrose, maltose, dextrin, dried invert sugar,fructose, levulose, galactose, corn syrup solids, and the like, alone orin combination.

Sugarless sweeteners include, e.g., sugar alcohols such as sorbitol,mannitol, xylitol, hydrogenated starch hydrolysates, maltol, and thelike, alone or in combination.

High intensity artificial sweeteners can also be used, alone or incombination with the above. Non-limiting examples of such sweetenersinclude sucralose, aspartame, salts of acesulfame, alitame, saccharinand its salts, cyclamic acid and its salts, glycyrrhizin,dihydrochalccones, thaumatin, monellin, and the like, alone or incombination. To provide longer lasting sweetness and flavor perception,it may be desirable to encapsulate or otherwise control the release ofat least a portion of the artificial sweetener. Such techniques as wetgranulation, wax granulation, spray drying, spray chilling, fluid bedcoating, coacervation, and fiber extension may be used to achieve thedesired release characteristics.

The amount of the artificial sweetener used will vary greatly and willdepend on such factors as potency of the sweetener, rate of release,desired sweetness of the product, level and type of flavor used, andcost considerations. Thus, the active level of the artificial sweetenermay vary from about 0.02% to about 8.0% by weight. When carriers usedfor encapsulation are included, the amount of the encapsulated sweetenerused will be proportionately higher.

The chewing gum of this invention may be either sugarless orsugar-containing. Alternatively, the chewing gum may containcombinations of sugar and/or sugarless sweeteners. While ordinarysugars, e.g., sucrose, can be used in the invention, it is preferable toavoid them because of their cariogenic nature. Non-fermentable sugarssuch as sorbitol are preferred. Additionally, a softener may be addedwhich provides additional sweetness such as with aqueous sugar oralditol solutions.

If a low calorie gum is desired, a low caloric bulking agent can beused. Non-limiting examples of such low calorie bulking agents includepolydextrose, raftilose, raftilin, fructooligosaccharides, palatinoseoligosaccharides, guar gum hydrolysates, or indigestible dextrin.

Suitable flavoring agents include those which have been previouslydescribed herein.

The flavoring agent can be used in the chewing gum of this invention inan amount preferably ranging from about 0.1% to about 15.0% by weight,more preferably from about 0.2% to about 5.0% by weight.

The chewing gum may also contain a dental abrasive. Dental abrasives areparticularly valuable in chewing gums because of the polishing actionwhich occurs during chewing. The term “dental abrasives” as used hereinincludes all manner and form of such materials which are normally usedin toothpastes, chewing gums and the like. The preferred dental abrasivefor use in this invention is dicalcium diphosphate dihydrate, which alsoserves as an alkaline buffer. Other non-limiting examples of suitabledental abrasives include calcium carbonate, sodium metaphosphate,aluminum hydroxide, magnesium carbonate, calcium sulphate, silicas suchas aerogels and xerogels, and tricalcium phosphate. The dental abrasiveis preferably used in an amount of from about 1.0% to about 30.0% byweight, more preferably from about 1.5% to about 20.0% by weight.

The chewing gum of this invention may also contain glycerine, whichserves to soften and maintain the chewability of the chewing gum forprolonged periods and also adds to the sweetness of the chewing gum. Theglycerine is preferably used in an amount of from about 0.01% to about10.0% by weight, more preferably from about 0.2% to about 5.0% by weightof the chewing gum.

EXPERIMENTAL

Examples 1-4 illustrate agglomerated compositions which can be used inthe remineralizing chewing gums of the present invention.

EXAMPLE 1

In Example 1, cationic and anionic agglomerate particles are preparedfrom the ingredients set forth in Table I below.

TABLE I Example 1: Agglomerate Particle Ingredients Cationic PartAnionic Part Ingredient (wt. %) (wt. %) Sorbitol 60.00 60.00 CalciumAcetate 40.00 0 Monosodium Orthophosphate 0 40.00

The ingredients in the cationic part are initially mixed and compressedby any means, e.g., passage through a chilsonator (Fitzpatrick) to forma solid sheet or passage through a tablet press. The resulting solidmaterials are then ground to a desirable particle size of from about 50to about 500 microns.

Similarly, the ingredients in the anionic part are mixed and compressedin the same manner as was done with the ingredients in the cationicpart, the resulting solid materials also being ground to a desirableparticle size of from about 50 to about 500 microns.

The agglomerated cationic and anionic particles are then added to aconventional chewing gum base to form a chewing gum product containingabout 2.5% by weight of the cationic particles, about 2.5% by weight ofthe anionic particles, and about 95.0% by weight of the conventionalchewing gum ingredients.

EXAMPLE 2

In Example 2, cationic and anionic agglomerate particles are preparedfrom the ingredients set forth in Table II below.

TABLE II Example 2: Agglomerate Particle Ingredients Cationic PartAnionic Part Ingredient (wt. %) (wt. %) Sorbitol 40.00 50.00 Xylitol20.00 0 Malic Acid 0 5.00 Calcium Lactate 40.00 0 Monoammonium Phosphate0 45.00

The mixing and compressing steps followed in Example 1 above arerepeated in Example 2. The solid materials formed from the mixing andcompressing of the cationic part ingredients are ground to a particlesize of from about 50 to about 500 microns. Likewise, the solidmaterials formed from the mixing and compressing of the anionic partingredients are also ground to a particle size of from about 50 to about500 microns.

The agglomerated cationic and anionic particles are then added to aconventional chewing gum base to form a chewing gum product containingabout 8.0% by weight of the cationic particles, about 2.0% by weight ofthe anionic particles, and about 90.0% by weight of the conventionalchewing gum ingredients.

EXAMPLE 3

In Example 3, cationic and anionic agglomerate particles are preparedfrom the ingredients set forth in Table III below.

TABLE III Example 3: Agglomerate Particle Ingredients Cationic PartAnionic Part Ingredient (wt. %) (wt. %) Sorbitol 40.00 60.00 Mannitol20.00 0 Sodium Bicarbonate 0 5.00 Calcium Sulfate 40.00 0 DipotassiumPhosphate 0 35.00

The mixing and compressing steps followed in Examples 1 and 2 above arerepeated in Example 3, with the solid materials formed from the cationicand anionic part ingredients being ground to a desirable particle sizeof between about 50 and about 500 microns.

The agglomerated cationic and anionic particles are then added to aconventional chewing gum base to form a chewing gum product containingabout 6.0% by weight of the cationic particles, about 4.0% by weight ofthe anionic particles, and about 90.0% by weight of the conventionalchewing gum ingredients.

EXAMPLE 4

In Example 4, cationic and anionic agglomerate particles are preparedfrom the ingredients set forth in Table IV below.

TABLE IV Example 4: Agglomerate Particle Ingredients Cationic PartAnionic Part Ingredient (wt. %) (wt. %) Carbowax 8000 25.00 30.00Xylitol 10.00 0 Calcium Chloride 65.00 0 Monopotassium Phosphate 0 70.00

The mixing and compressing steps followed in Examples 1, 2 and 3 arerepeated in Example 4. The solid particles are ground to a particle sizeof between about 50 and about 500 microns.

The agglomerated cationic and anionic particles are then added to aconventional chewing gum base to form a chewing gum product containingabout 5.0% by weight of the cationic particles, about 2.0% by weight ofthe anionic particles, and about 93.0% by weight of the conventionalchewing gum ingredients.

What is claimed is:
 1. A chewing gum product capable of effectingremineralization of subsurface dental lesions and/or mineralization ofexposed dentinal tubules, comprising: (A) a discrete cationicagglomerate component comprising at least one water-soluble or partiallywater soluble calcium salt and a first inert solid carrier; (B) adiscrete cationic agglomerate component comprising at least one watersoluble orthophosphate salt and a second inert solid carrier; and (C) agum base containing said components (A) and (B); wherein components (A)and (B) have a pH in water such that a mixed aqueous solution formed bymixing components (A) and (B) with water and/or saliva has a pH of fromabout 4.50 to about 10.0; further wherein the cationic and anionicagglomerate components keep said calcium salt and said orthophosphatesalt from reacting prior to use and are simultaneously releasable fromthe gum base upon mixing of the product with water and/or saliva to formthe mixed aqueous solution such that the mixed aqueous solutioncomprises calcium cations released from the calcium salt andorthophosphate anions released by the orthophosphate salt.
 2. A productaccording to claim 1, wherein one or both of the first and second solidinert carriers is selected from the group consisting of sorbitol,mannitol, and xylitol.
 3. A product according to claim 1, wherein one orboth of the first and second solid inert carriers is an insoluble silicaor an insoluble calcium phosphate.
 4. A product according to claim 3,wherein the insoluble calcium phosphate is selected from the groupconsisting of dicalcium phosphate dihydrate, anhydrous dicalciumphosphate, tricalcium phosphate and calcium hydroxyapatite.
 5. A productaccording to claim 1, wherein one or both of the cationic and anionicagglomerate components further comprises a binder.
 6. A productaccording to claim 5, wherein said binder is a polymer selected from thegroup consisting of polyvinyl acetate, PVP and carboxymethyl cellulose.7. A product according to claim 1, wherein the cationic and anionicagglomerate components each have an average particle size ranging fromabout 20 to about 500 microns.
 8. A product according to claim 1,wherein the cationic and anionic agglomerate components each have anaverage particle size ranging from about 30 to about 100 microns.
 9. Aproduct according to claim 1, wherein the product has a smoothconsistency and the cationic and anionic agglomerate components eachhave an average particle size of from about 30 to about 50 microns. 10.A product according to claim 1, wherein the product has a crunchyconsistency and the cationic and anionic agglomerate components eachhave an average particle size of from about 50 to about 80 microns. 11.A product according to claim 1, wherein components (A) and (B) have a pHin water such that the mixed aqueous solution has a pH of from about 5.0to about 8.0.
 12. A product according to claim 1, wherein components (A)and (B) have a pH in water such that the mixed aqueous solution as a pHof from about 5.5 to about 7.0.
 13. A product according to claim 1,wherein the calcium salt is a water-soluble calcium salt selected fromthe group consisting of calcium chloride, calcium nitrate, calciumacetate, calcium lactate, calcium gluconate, and mixtures thereof.
 14. Aproduct according to claim 1, wherein the calcium salt is calciumnitrate.
 15. A product according to claim 1, wherein the calcium salt isa partially water-soluble calcium salt selected from the groupconsisting of calcium sulfate, anhydrous calcium sulfate, calciumsulfate hemihydrate, calcium sulfate dihydrate, calcium malate, calciumtartarte, calcium malonate and calcium succinate.
 16. A productaccording to claim 1, wherein the calcium salt is calcium sulfate.
 17. Aproduct according to claim 1, wherein the orthophosphate salt isselected from the group consisting of alkali metal salts oforthophosphoric acid and ammonium salts of orthophosphoric acid.
 18. Aproduct according to claim 1, wherein the orthophosphate salt isselected from the group consisting of potassium orthophosphate, sodiumorthophosphate, ammonium orthophosphate, monopotassium orthophosphate,dipotassium orthophosphate, tripotassium orthophosphate, monosodiumorthophosphate, disodium orthophosphate and trisodium orthophosphate.19. A product according to claim 1, wherein the cationic agglomeratecomponent further comprises at least one non-toxic divalent metal saltother than a calcium salt.
 20. A product according to claim 1, whereinthe anionic agglomerate component further comprises at least onewater-soluble fluoride salt.